Adult stem cells appear to be remarkably flexible in their ability to reconstitute different tissue lineages raising great interest in assessing the therapeutic potential of those stem cells. For example in skin in vivo both inter-follicular epidermis and hair follicle stem cells can actively participate in wound-healing. Even though hair follicle stem cells are one of the best-characterized adult stem cells system still very little is known about the other stem cells in different skin appendages like sweat glands. It is very likely that these separate skin appendages have their own stem cells which probably could share common molecular features to maintain their stem cells characteristics as well as they presumably are regulated by distinct environmental signals which control their local specification or fate. Thus the main aspect of the proposed research is to test the hypothesis if in adult skin alternative stem cells exist in the areas where hair follicle stem cells are missing. Therefore we will utilize the H2B-GFP system for in vivo detection of infrequently dividing cells to check whether there are different skin stem cells which reside outside of hair follicle niche. This system will allow us not only to localize and isolate those cells but as well for the first time characterize the live stem cells from sweat glands and compare common and unique features of these stem cells to the well- characterized hair follicle stem cells. The comparison between different adult skin stem cells might be highly instructive to study the mechanisms that underlie stem cells niche homeostasis. These data would be also very helpful to understand how different microenvironmental signals in the niche determine the mechanism of stem cell plasticity or tissue-specific regeneration. In long term this knowledge would be useful to translate these basic discoveries to novel form of stem cell therapy with application in human for example in regenerative skin healing and different genetic skin disorders. Overall goal is to understand very basic processes that are important for different skin stem cell niches regulation.